The goal of this application is to understand the roles of the main and accessory olfactory systems in mediating appetitive social behaviors in mice. It has been well established that various chemosensory cues and in particular pheromones, are important triggers for social behaviors. The vast majority of such chemosensory cues are processed through one of two olfactory systems, either the main olfactory system (MOS) or the accessory olfactory system (AOS). The reigning dogma has always been that the AOS is the system by which pheromones are detected and processed; whereas, the MOS is important for detecting and processing most "normal" odorants. This distinction, however, is no longer clear. There are now numerous examples in mammals of the MOS detecting and processing pheromonal cues. This study aims to define the relative roles of the MOS and the AOS in mediating appetitive social behavior in mice. This study will take advantage of two recently generated lines of transgenic mice with targeted deletions of proteins critical for the function of either the MOS or AOS. A targeted deletion of the cyclic nucleotide gated ion channel subunit A2 (CNGA2 null) makes mice anosmic to most "normal" odorants. A targeted deletion of the transient receptor potential channel subunit 2 (TRP2 null) eliminates most if not all activity of the vomeronasal organ, the sensory organ of the AOS. This study has two main components. First, it will test mice using combination of operant and preference tests, which will delineate between an animal's ability to discriminate chemosensory cues and their motivation to respond to these biologically relevant cues. In using these tests on TRP2 null and CNGA2 null mice the experiments will provide significant evidence for the central hypothesis that the MOS and not the AOS is crucial for mediating appetitive social behaviors in mice. Second, using the immediate early gene c-fos as a marker for neuronal activation it will examine differences in the processing of chemosensory cues, derived from male and female urine, between TRP2 null, CNGA2 null and wild-type mice.